Xenobiotic induction of liver peroxisomes is associated with hypolipidemia. To test the involvement of the peroxisome proliferation with the hypolipidemia, male rats were inoculated in the groin with five different
tumors: an
aflatoxin-induced
hepatoma, a
lasiocarpine-induced
hepatoma, an
actinomycin-D-induced
mesothelioma, a
lasiocarpine-induced
squamous cell carcinoma, and a
methylnitrosourea-induced
fibrosarcoma. After the tumours reached a suitable size, the rats were fed diets containing the peroxisome-proliferating
hypolipidemic agents tibric acid (2-chloro-5-[3,5-dimethylpiperidinosulfonyl]
benzoic acid) or
Wy-14,643 ([4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]
acetic acid) for 2 weeks. Liver and
tumor tissues were then assayed for the peroxisome-associated
enzymes,
catalase and
carnitine acetyltransferase, and correlated with serum levels of
triglyceride and
cholesterol. The presence of the
tumors caused a predictable decrease in liver
catalase and a slight elevation of liver
carnitine acetyltransferase. Serum
cholesterol was elevated slightly, while serum
triglyceride levels were elevated, unchanged, or decreased in the
tumor-bearing rats maintained on control diet. Inclusion of the
xenobiotics in the diet caused increases in liver weight,
catalase, and
carnitine acetyltransferase. Serum
triglycerides were decreased in the three groups which were not already decreased, but a decrease in serum
cholesterol was only found in one group after only one of the treatments. The latter finding demonstrates that peroxisomal enzyme induction can be dissociated from the decrease in serum
cholesterol. The data were further evaluated by testing for correlations between the changes in these components, comparing changes within groups and between groups. These correlations indicate an inverse
biological association between liver
catalase and serum
cholesterol and between liver
carnitine acetyltransferase and serum
triglyceride. The latter correlation was inverse only for comparisons between groups, suggesting that
carnitine acetyltransferase activity is associated with serum
triglycerides only during the perturbational state.